Periodontal disease is the most common cause of tooth loss in the adult human and it is therefore a massive public health problem. It is generally agreed that our best opportunity for solution of this problem lies in research aimed at prevention. One important aspect of this research is investigation of the response of the host's tissues to the etiologic agent(s) responsible for the disease. There is a large body of clinical, histopathologic and chemical evidence supporting the concept that the production, maturation and maintenance of the collagenous component of the periodontium may play a vital role in the function of the normal periodontium and that derrangement of the collagenous component does occur concomitantly with the development of periodontal disease. Maturation of connective tissues and development of a high degree of tensile strength are a result of the introduction of covalent interchain crosslinks in collagen. Thus, the degree of maturation of collagen of the periodontium and the mechanism by which it is crosslinked are of considerable interest in understanding factors underlying periodontal disease. The administration of lathyrogens inhibits the formation of crosslinks in both collagen and in elastin and their use has been a very valuable research tool in deciphering the crosslinking mechanism. It is now clear that one mechanism by which lathyrogens inhibit crosslinking is by inhibition of amine oxidase activity in collagen and elastin. However, this mechanism alone does not appear to fully explain the alterations seen in the tissues of the lathyritic animals. We propose to investigate the hypothesis that intermolecular and intramolecular crosslinking in collagen are inhibited both by the enzyme inhibition mechanism and by binding of the lathyrogen as Schiff base to these lysyl and hydroxylysyl side chains in collagen which are slated for participation in crosslink formation.